HeLa cells chronically infested with either coxsackievirus B3 or B5 were shown to acquire a specific resistance to superinfection by only those viruses belonging to coxsackievirus group B. This resistance was found to result from altered cell surfaces, since superinfecting group B virus did not attach or eclipse. These observations have served as a basis for continuation of the early interaction of enteroviruses with their specific receptors of host cells. Attempts will be made to characterize the extracted receptors from isolated plasma membranes of HeLa cells and to characterize the naturally occurring inhibitor of B3 virus uncoating activity which stabilizes the "A" particle which is formed following receptor activity on the virions. In addition, potential chemical inhibitors of coxsackievirus RNA uncoating will be screened in an attempt to find a useful chemotherapeutic compound for prevention or treatment of infection by these viruses. It is likely that one compound, which is active at the cell surface, would be useful for all group B coxsackieviruses, based on our evidence that there is a common group receptor for these viruses. Employing our recently developed method for obtaining substructures of coxsackievirus B3, plans are made to determine the functions of each of the four virion polypeptides. Recovery and analysis of the virion substructures may provide antigens useful for a rapid diagnostic test for detection of coxsackievirus infections and for the future development of a subunit virus vaccine. Plans are made to determine the molecular events in the pathogenesis of acute and chronic infections of mice with heart disease caused by coxsackievirus B3. It is anticipated that the coxsackievirus B3-HeLa cell carrier culture system developed earlier, will serve as a useful in vitro model in this phase of the program. In a related, but different sphere of activity, experiments are proposed to determine the mechanism for the unique susceptibility of differentiating myogenic cells in culture to infection by coxsackieviruses of group A. In view of our recent success with RD and L8 cells, efforts will be extended to obtain a cell line which would be useful for the isolation and identification of all of the members of the group A coxsackieviruses in the virus diagnostic laboratory.